Sterile and pyrogen-free water for injection (WFI) is an essential material for field medical operations requiring parenteral procedures. Producing, transporting, and storing sufficiently large amounts of WFI is a key logistical problem. This challenge necessitates the development of a compact, reliable, and automatic system that can continuously produce sterile and pyrogen-free WFI from potable water sources. Furthermore, sterile and pyrogen-free WFI can be used to produce intravenous (IV) fluids and reconstitute freeze-dried blood products. Such devices are particularly useful for ocean vessels to reduce shipboard WFI storage burdens.
The elimination of all living microorganisms (sterilization) and fever-causing agents i.e. pyrogens (depyrogenation) from water can be accomplished by physical methods (heat), chemical agents (ethylene oxide, formaldehyde, alcohol, ozone), radiation, or mechanical methods (filtration). Steam and dry heat are widely used means of sterilization, which can be achieved at temperatures of 121° C. (15 min.) and 180° C. (20 min.), respectively.
Pyrogens, or bacterial endotoxins, are either metabolic products of living microorganisms or the constituents of dead microorganisms. Chemically, pyrogens are lipopolysaccharides (LPS) with molecular weights ranging from 15,000 to several million. Both dry pyrogen extracts and pyrogenic aqueous solutions lose little or their activity over years. Therefore, depyrogenation requires satisfactorily high temperatures and long holding times. Some of the reported data indicate that 180° C. for 3 to 4 hours, 250° C. for 30 to 45 minutes, or 650° C. for 1 minute under any heat will destroy pyrogens.
In addition to sterilization and depyrogenation, injectable water must also be virtually free from particulate matter, oxidizable substances, dissolved gases, and metals. Currently, the only acceptable ways of manufacturing WFI are distillation and reverse osmosis (RO). However, both methods have limitations when intended for field deployment.
Although distillation is the oldest and most effective method to remove LPS, the distillation still operated under low pressures is bulky and heat recovery is limited. Distillation and reverse osmosis physically separate pyrogen from water but neither destroys the pyrogens. The pyrogens concentrated in the distillation still residues or reverse osmosis retentate must be purged continuously or intermittently from the system. To ensure consistent production of pyrogen-free water, the equipment must be periodically sterilized to destroy the residual pyrogens that would accumulate on the walls of the equipment.
As for RO, typically 99.5% to 99.9% of endotoxin load can be removed in a single pass, and RO filters are not absolute. To produce WFI, both of these methods require additional treatment steps, typically involving active carbon filters, deionizers, and ultrafiltration filters. There is currently a lack of a final heat sterilization method, which is currently required for FDA approval.